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Background: Statins increase T2D risk despite favorable effects on lipids, inflammation, and cardiovascular disease (CVD). Statins may modulate associations of T2D-related BCAAs with incident T2D.

Methods: JUPITER (NCT00239681) randomized rosuvastatin vs. placebo for primary CVD prevention. Plasma BCAAs (isoleucine, leucine, valine) and alanine were quantified via NMR spectroscopy for n=12,441 at baseline and n=9,826 with repeat 12mo samples. We calculated % change in metabolites with mixed effects linear regression. We used Cox models to evaluate baseline and change (per SD) of metabolites with incident T2D (multivariable-adj HR [95%CI]) during 2y of follow-up (max. 5y).

Results: Overall, statin vs. placebo increased T2D (HR 1.25 [95% CI: 1.05-1.49]). BCAA metabolites changed modestly at 12mo; only leucine differed with statin vs. placebo (+3.7% vs. +2.4%; p=0.03). Baseline BCAAs were associated with T2D. Each SD increase in isoleucine, leucine, valine, and alanine was associated with HR=1.3 (1.1-1.5), 1.1 (1.0, 1.3), 1.3 (1.1, 1.5), and 1.3 (1.1, 1.5) greater T2D risk (FIGURE). Associations did not differ with statin vs. placebo.

Conclusion: High-intensity statin therapy had at most modest effects on BCAA metabolites. Baseline and change in BCAAs and alanine were associated with T2D, including during randomized statin therapy.

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Disclosure

D. K. Tobias: None. P. Ridker: Consultant; Self; 360 Marketing Strategic Services, AstraZeneca, Corvidia Therapeutics, CSL Behring, DalCor Pharmaceuticals, Novartis AG, Omeicos, Flame, Uppton, Agepha, sIRNAomics, Research Support; Self; Amarin Corporation plc, Kowa Pharmaceuticals America, Inc., Novo Nordisk. R. Glynn: Research Support; Self; AstraZeneca, Kowa Research Institute, Inc., Novartis AG, Pfizer Inc. S. Mora: Consultant; Self; Pfizer Inc., Quest Diagnostics, Other Relationship; Self; LabCorp.

Funding

American Diabetes Association (1-19-JDF-115 to D.K.T.); Brigham and Women’s Hospital (to D.K.T.); National Institutes of Health (R01HL117861, R01HL134811, K24HL136852, R01DK112940 to S.M.); LabCorp

© 2021 by the American Diabetes Association
2021
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